2. Drugs & Chemicals Poisoning
By Dr. Jamshidi

3. Management of overdose and poisoning

4. General- evaluation Rcognition of poisoning
Identification of agents involved
Assessment of severity
Prediction of toxicity

5. General- management provision of supportive care
prevention of poison absorption
Enhancement of elimination of
poison
Administration of antidotes

6. Supportive care
A: First, the airway should be cleared of vomitus or any other obstruction and an oral airway or endotracheal tube inserted if needed.
B: Breathing should be assessed by observation and oximetry and, if in doubt by measuring arterial blood gases patients with respiratory insufficiency should be intubated and mechanically ventilated

7. Supportive care
C: Circulation should be assessed by continuous monitoring of:
- pulse rate
- blood pressure
-urinary output
An intravenous line should be placed and blood drawn fro serum glucose and other routine determinations
Dextrose to treat hypoglycemia (0.5gm/kg)

8. Supportive care Vital signs, mental status, and pupil size
Pulse oximetry, cardiac monitoring, ECG
Protect airway
Intravenous access
cervical immobilization if suspect trauma
Rule out hypoglycaemia
Naloxone for suspected opiate poisoning

9. History Pill bottles Alcohol Drug history including access
Remember OTC drugs
Suicide note
National Poisons Information Centre (09694)

10. Examinations Drug Physiologic excitation : Physiologic depression
anticholinergic
sympathomimetic
central hallucinogenic agents
drug withdrawal
Physiologic depression
cholinergic (parasympathomimetic)
sympatholytic
opiate, or sedative-hypnotic agents, or alcohols
Mixed state –
polydrugs, hypoglycemic agents, tricyclic antidepressants, salicylates, cyanide

11. Drug detection

12. Drug levels

13. Preventing absorption
Gastric lavage
Not in unconscious patient unless intubated (risk aspiration)
Flexible tube is inserted through the nose into the stomach
Stomach contents are then suctioned via the tube
A solution of saline is injected into the tube
Recommended for up to 2 hrs in TCA & up to 4hrs in Salicylate OD
Induced Vomiting
Ipecac - Not routinely recommended
Risk of aspiration

14. CONTRAINDICATION OF EMESIS
Corrosives and volatile poisons
Comatose patients
Heart disease patients
Pregnant women
Kerosene : may cause aspiration pneumonia
Convulsant patients

15. Preventing absorption
Activated charcoal
Adsorbs toxic substances or irritants, thus inhibiting GI absorption
Addition of sorbitol →laxative effect
Oral: g as a single dose
Repetitive doses useful to enhance the elimination of certain drugs:
-theophylline
-phenobarbital
- carbamazepine
- aspirin
-sustained-release products

16. Preventing absorption
not effective for:
- cyanide
-mineral acids
-caustic alkalis
- organic solvents
-iron, ethanol, methanol poisoning, lithium

17. Elimination of poisons
Renal elimination
Medication to stimulate urination or defecation may be given to try to flush the excess drug out of the body faster
Forced alkaline diuresis
Infusion of large amount of NS+NAHCO3
Used to eliminate acidic drug that mainly excreted by the kidney eg salicylates
CAUTIONS
Serious fluid and electrolytes disturbance may occur
Need expert monitoring

18. Elimination of poisons
Hemodialysis or haemoperfusion:
Reserved for severe poisoning
Drug should be dialyzable i.e. protein bound with low volume of distribution
may also be used temporarily or as long term if the kidneys are damaged due to the overdose.

19. Hemoperfusion

20. Antidotes Does an antidote exist?
Does actual or predicted severity of poisoning warrant its use?
Do expected benefits of therapy outweigh its associated risk?
Are there contraindications?

21. Specific overdoses

22. Opiates Opiat poisoning Antidote – naloxone
MoA: Pure opioid antagonist competes and displaces narcotics at opioid receptor sites
I.V. (preferred), I.M., intratracheal, SubQ: mg every 2-3 minutes as needed
Lower doses in opiate dependence

23. Opiates Elimination half-life of naloxone is only 60 to 90 minutes
Repeated administration/infusion may be necessary
Side Effects
BP changes; arrhythmias; seizures;
withdrawal syndrome

24. Benzodiazepines Benzodiazepine poisoning Antidote – flumazenil
MoA: Benzodiazepine antagonist
IV administration 0.2 mg over 15 sec to max 3mg
S/E : arrhythmias; convulsions
C/I concomitant TCAD; status epilepticus
Should not be used for making the diagnosis
Benzodiazepines may be masking/protecting against other drug effects

25. Tricyclic antidepressants
PHARMACOLOGY —
TCAs have several important cellular effects, including inhibition of:
    -Presynaptic neurotransmitter reuptake     -Cardiac fast sodium channels     -Central and peripheral muscarinic acetylcholine receptors     -Peripheral alpha-1 adrenergic receptors     -Histamine (H1) receptors     -CNS GABA-A receptors

26. TCAD overdose clinical features
Arrhythmias
- widening of PR, QRS, and QT intervals;
- heart block
Hypotension
Anticholinergic toxicity
- hyperthermia
- flushing
-dilated pupils
-intestinal ileus
-urinary retention
- sinus tachycardia
Confusion, delirium, hallucinations
Seizures

27. TCAD overdose Diagnosis
History
Blood/urine toxicology screen

28. TCAD overdose -Treatment
many require intubation
Consider gastric lavage if taken < 2hrs
Activated charcoal
Treatment of hypotension with isotonic saline
Sodium bicarbonate for cardiovascular toxicity
Alpha adrenergic vasopressors (norepinephrine ) Benzodiazepines for seizures

29. Sodium Bicarbonate in TCA overdose
Hypertonic sodium bicarbonate (NaHCO3)
- QRS widening >100 msec
-ventricular arrhythmias
-refractory hypotension
↑ serum pH promotes protein binding and ↓ free drug concentrations

30. Sodium Bicarbonate in TCA overdose
reasonable goal pH is 7.50 to 7.55 then taper dose
S/E:
Volume overload
hypernatreamia
metabolic alkalosis

31. Special Cautions in TCAD overdose
Class IA and IC antiarrhythmic agents are contraindicated eg:
quinidine
Disopyramide
Flecainide
propafenone
Class IB Lignocaine, phenytoin used
Phenytoin may precipitate arrhythmias
Magnesium may be useful
Flumazenil must not be given

32. Salicylate overdose Aspirin (acetylsalicylic acid)
Methyl salicylate (Oil of Wintergreen)
5 ml = 7g salicylic acid
Herbal remedies
Fatal intoxication can occur after the ingestion of 10 to 30 g by adults and as little as 3 g by children

33. Salicylate levels -Rapidly absorbed
-peak blood levels usually occur within one hour but delayed in overdose 6-35 hrs plasma salicylate concentration
4 hrs post ingestion & every 2 hrs until they are clearly falling
Most patients show signs of intoxication when the plasma level exceeds 40 to 50 mg/dL (2.9 to 3.6 mmol/L)

34. Salicylate overdose
1- Inhibition of cyclooxygenase results in decreased synthesis of prostaglandins, prostacyclin, and thromboxanes
2- Stimulation of the chemoreceptor trigger zone in the medulla causes:
nausea and vomiting
3- Activation of the respiratory center of the medulla results in:
tachypnea, hyperventilation, respiratory alkalosis
4- Uncoupled oxidative phosphorylation in the mitochondria generates heat and may increase body temperature
5- Interference with cellular metabolism leads to metabolic acidosis

35. Clinical features Early symptoms of aspirin toxicity include: tinnitus
Fever
Vertigo
Nausea
Hyperventilation
Vomiting
diarrhoea
More severe intoxication can cause:
altered mental status, coma
non-cardiac pulmonary edema and death

36. Metabolic abnormalities
Stimulate the respiratory center directly, early fall in the PCO2 and respiratory alkalosis
An anion-gap metabolic acidosis then follows, due to the accumulation of organic acids, including lactic acid and ketoacids
Mixed respiratory alkalosis and metabolic acidosis with ↑ anion gap
Arterial Ph variable depending on severity

37. Metabolic abnormalities
Metabolic acidosis increases the plasma concentration of protonated salicylate
thus worsening toxicity by allowing easy diffusion of the drug across cell membranes

38. Salicylate overdose - treatment
directed toward increasing systemic pH by the administration of sodium bicarbonate
IV fluids +/- vasopressors
Supplemental glucose (100 mL of 50 percent dextrose in adults) to patients with altered mental status regardless of serum glucose concentration to:
overcome neuroglycopaenia
Hemodialysis

39. Alkalinization of plasma and urine
Alkalemia from a respiratory alkalosis is not a contraindication to sodium bicarbonate therapy
A urine pH of 7.5 to 8.0 is desirable
Blood gas analysis every two hours
Avoid severe alkalemia (arterial pH >7.60)

40. Haemodialysis - indications
Altered mental status
Pulmonary or cerebral edema
Renal insufficiency that interferes with salicylate excretion
Fluid overload that prevents the administration of sodium bicarbonate
A plasma salicylate concentration >100 mg/dL
Clinical deterioration despite aggressive and appropriate supportive care

41. Paracetamol Widely available Potential toxicity underestimated
Toxicity unlikely to result from a single dose of less than 150 mg/kg in child or 7.5 to 10 g for adult
Toxicity is likely with single ingestions greater than 250 mg/kg or those greater than 12 g over a 24-hour period
Virtually all patients who ingest doses in excess of 350 mg/kg develop severe liver toxicity unless appropriately treated

43. Factors influencing toxicity
Dose ingested
Excessive cytochrome P450 activity due to induction by chronic alcohol or other drug use eg carbamazepine, phenytoin, isoniazid, rifampin
Decreased capacity for glucuronidation or sulfation
Depletion of glutathione stores due to malnutrition or chronic alcohol ingestion
Acute alcohol ingestion is not a risk factor for hepatotoxicity and may even be protective by competing with acetaminophen for CYP2E1

44. Clinical features Stage I (0.5 to 24 hours) No symptoms
Stage II (24 to 72 hours)
Subclinical elevations of hepatic aminotransferases (AST, ALT)
-right upper quadrant pain
-liver enlargement and tenderness
-Elevations of prothrombin time (PT)
-oliguria and renal function abnormalities may become evident

45. Clinical features Stage III (72 to 96 hours) -Jaundice
-confusion (hepatic encephalopathy)
-marked elevation in hepatic enzymes
-hyperammonemia
lactic acidosis-
- renal failure 25%
- death
Stage IV (4 days to 2 weeks)
Recovery phase that usually begins by day 4 and is complete by 7 days after overdose

46. Paracetamol overdose
The risk of toxicity is best predicted by relating the time of ingestion to the serum paracetamol concentration
Peak serum concentrations reached within 4 hrs following overdose of immediate-release preparations
May be delayed with extended releases preparations or drugs that delay gastric emptying (eg, opiates, anticholinergic agents) are coingested
Check level at >= 4 hrs

47. Paracetamol overdose treatment
Activated charcoal within four hours of ingestion
May reduce absorption by 50 to 90 percent
Single oral dose of one gram per kilogram
Inhibits absorption of oral methionine

48. Activated Charcoal

49. N-acetylcysteine Antidote – MOA: a glutathione precursor
Limits the formation and accumulation of NAPQI
Powerful anti-inflammatory and antioxidant effects
IV infusion or oral tablets (also oral methionine)
150mg/Kg over 15 min; 50mg/Kg over next 4 hrs; 100mg/kg over next 16 hrs up to 36hrs
Beyond 8 hours, NAC efficacy progressively decreases
S/Es nausea, flushing, urticaria, bronchospasm, angioedema, fever, chills, hypotension, hemolysis and rarely, cardiovascular collapse

50. Paracetamol overdose treatment
At the end of NAC infusion, a blood sample should be taken for determination of the INR, plasma creatinine and ALT.
If any is abnormal or the patient is symptomatic, further monitoring is required and advice sought from the NPIS
Patients with normal INR, plasma creatinine and ALT and who are asymptomatic may be discharged from medical care.
They should be advised to return to hospital if vomiting or abdominal pain develop or recur

51. Indications for liver transplantation
Liver transplantation is life-saving for fulminant hepatic necrosis
The indications for liver transplantation are:
1 - Acidosis (pH < 7.3), or
2 - PT > 100 sec
3 - Creatinine > 300 mcg/l
4 - Grade 3 encephalopathy (or worse)
It is better to contact the local liver transplant centre earlier than this.
Grossly abnormal prothrombin times should trigger referral:
PT > 20 sec at 24 hr
PT > 40 sec at 48 hr

52. Alcohol poisoning
Clinical features of acute alcohol poisoning include:
Ataxia and anaesthesia leading to accidental injury
Dysarthria and nystagmus
Drowsiness which may progress to coma
Inhalation of vomit which can be fatal & should be prevented
Hypoglycaemia in children and some adults
Check BG TEST and give 50% glucose i.v. if required

53. Coma (alcohol induced)
In cases of alcohol induced coma exclude:
Coincident head injury
Hepatic failure
Meningitis
Wernicke’s encephalopathy
Other associated drug ingestion
A blood test will confirm substantial levels of alcohol
Rule out alcoholic hypoglycaemia
The airway and circulation must be maintained
But glucose- containing fluids may precipitate Wernicke's encephalopathy
Thiamine should given to all
Intravenous naloxone has reversed coma in a proportion of cases

59. Any Question?